The objective of this proposal is to extend our current studies which have suggested a role of mammalian liver in the renewal of erythrocyte purine nucleotides. We have shown by in situ perfusion of rabbit liver that adenosine, formed in the liver cell and released by that cell, is readily taken up by perfused human erythrocytes and converted to adenine nucleotides. Adenosine, released from labeled rabbit liver slices also serves as a precursor of human and rabbit erythrocyte adenine nucleotides in vitro. These finding suggest a mechanism for the turnover of adenine nucleotides in the mammalian erythrocyte, known to lack the de novo pathway for purine nucleotide biosynthesis, and for the maintenance of the concentrations of the adenine nucleotides, essential for the viability of the cell. It is proposed to extend the current study in order to investigate: 1) Transfer of labeled purine compounds from rabbit liver to rabbit erythrocyte by in situ perfusion. 2) Utilization of rabbit liver adenosine as a direct precursor of adenine nucleotides in rabbit erythrocytes and other cells and tissues, in vivo (e.g. bone marrow, leukocytes, platelets). 3) Mammalian erythrocyte as a possible transporter of purine compounds to other tissues. 4) Metabolic origin of adenosine release from hepatic cell. 5) Formation of purine nucleosides and release from human liver, in vitro.